Glia play a crucial role in providing metabolic support to neurons across different species. To do so, glial cells isolate distinct neuronal compartments from systemic signals and selectively transport specific metabolites and ions to support neuronal development and facilitate neuronal function. Because of their function as barriers, glial cells occupy privileged positions within the nervous system and have also evolved to serve as signaling intermediaries in various contexts. The fruit fly, Drosophila melanogaster, has significantly contributed to our understanding of glial barrier development and function. In this review, we will explore the formation of the glial sheath, blood-brain barrier, and nerve barrier, as well as the significance of glia-extracellular matrix interactions in barrier formation. Additionally, we will delve into the role of glia as signaling intermediaries in regulating nervous system development, function, and response to injury.